含有De Novo Carborane的宏环针对人体表皮生长因子受体
Yizhen Yin1, Nobuaki Ochi2, Timothy W Craven3
1Department of Chemistry, School of Science , The University of Tokyo , 7-3-1 Hongo , Bunkyo , Tokyo 113-0033 , Japan.
Journal of the American Chemical Society
|November 23, 2019
概括
人工氨基酸l-carboranylalanine (L-Cba) 可以启动合成,但不能延长. 研究人员设计了含有L-Cba的宏环,与人体表皮生长因子受体 (hEGFR) 结合,显示出用于癌症治疗和中子捕获治疗的潜力.
科学领域:
- 生物化学
- 合成生物学
- 医学化学
背景情况:
- 碳氨酸 (L-Cba) 是一种具有独特丰富集群的人工氨基酸.
- 其独特的化学特性引发了与核糖体翻译机制的兼容性问题.
研究的目的:
- 为了研究L-Cba在核糖体中被纳入.
- 开发针对人类表皮生长因子受体 (hEGFR) 的新型碳酸含有宏环.
主要方法:
- 使用flexizyme辅助的翻译系统研究合成过程中的L-Cba结合.
- 通过修改的L-Cba (ClAc-L-Cba) 进行hEGFR结合的设计和选择的宏环.
- 使用计算建模和基于细胞的测试来验证相互作用和准能力.
主要成果:
- 在核糖体合成的启动阶段,L- Cba的结合是成功的,但不是延长阶段,这可能是由于硬质阻碍.
- 两种选择的宏环对hEGFR具有很高的亲和力 (16和20nMK_D).
- 用光素标记的特异性染色hEGFR表达细胞,证实向输送.
结论:
- 可以通过L-Cba启动核糖体合成,从而产生新的含有碳酸的.
- 开发了针对hEGFR等瘤生物标志物的宏环新发现策略.
- 这些发现有望在癌症诊断和中子捕获疗法 (BNCT) 中应用.
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